Triethylamine → (11S)-11-Methyl-3-[(1E)-3-morpholin-4-yl-3-oxoprop-1-enyl]-10,11-dihydro-8H-[1,4]oxazino[4',3':1,2]imidazo[4,5-c]quinolin-6-amine

HRID 221628

反応式

HRID 221628 の反応式
C1(C)C=CC=CC=1P(C1C=CC=CC=1C)C1C=CC=CC=1C.C(N(CC)CC)C.Br[C:31]1[CH:40]=[C:39]2[C:34]([C:35]3[N:44]4[C@@H:45]([CH3:49])[CH2:46][O:47][CH2:48][C:43]4=[N:42][C:36]=3[C:37]([NH2:41])=[N:38]2)=[CH:33][CH:32]=1.[C:50]([N:54]1[CH2:59][CH2:58][O:57][CH2:56][CH2:55]1)(=[O:53])[CH:51]=[CH2:52].C([O-])([O-])=O.[K+].[K+]>CN(C=O)C.C([O-])(=O)C.[Pd+2].C([O-])(=O)C.C(Cl)(Cl)Cl.C(Cl)Cl>[CH3:49][C@@H:45]1[N:44]2[C:35]3[C:34]4[C:39](=[CH:40][C:31](/[CH:52]=[CH:51]/[C:50]([N:54]5[CH2:59][CH2:58][O:57][CH2:56][CH2:55]5)=[O:53])=[CH:32][CH:33]=4)[N:38]=[C:37]([NH2:41])[C:36]=3[N:42]=[C:43]2[CH2:48][O:47][CH2:46]1

参加物

10

反応物 5

HCID 8471TriethylamineHCID 11430Potassium CarbonateHCID 80271Tri-o-tolylphosphineHCID 98723AcryloylmorpholineHCID 58406168(11S)-3-bromo-11-methyl-10,11-dihydro-8H-[1,4]oxazino[4',3':1,2]imidazo[4,5-c]quinolin-6-amine

生成物 1

HCID 58406173(11S)-11-Methyl-3-[(1E)-3-morpholin-4-yl-3-oxoprop-1-enyl]-10,11-dihydro-8H-[1,4]oxazino[4',3':1,2]imidazo[4,5-c]quinolin-6-amine収率 63.5%

試薬・触媒・溶媒 4

HCID 167845palladium(II) acetate触媒HCID 6212Chloroform溶媒HCID 6228Dimethylformamide溶媒3 回HCID 6344Dichloromethane溶媒

反応条件

温度
120 °C

実験手順

A scintillation vial was charged with palladium acetate (22 mg, 0.10 mmol), tri-o-tolylphosphine (61 mg, 0.20 mmol), anhydrous DMF (1.0 mL) and triethylamine (0.4 mL, 3.0 mmol). The orange homogeneous solution was then added to a solution of (11S)-3-bromo-11-methyl-10,11-dihydro-8H-[1,4]oxazino[4′,3′:1,2]imidazo[4,5-c]quinolin-6-amine (333 mg, 1.00 mmol) dissolved in 10 mL of anhydrous DMF followed by the addition of a solution of 4-acryloylmorpholine (169 mg, 1.20 mmol) dissolved in 1.0 mL of anhydrous DMF. The mixture was transferred to a glass vessel and the vessel was purged with N2, sealed and heated to 120° C. for 18 hours. The reaction mixture was cooled and concentrated to dryness under reduced pressure to give a golden solid. The solid was treated with CH2Cl2 and saturated aqueous K2CO3 solution and the layers were separated. The organic layer was concentrated to dryness to give a light-brown solid. Chromatography (SiO2, 0-15% CMA/CHCl3) gave a tan solid that was crystallized from acetonitrile to give 250 mg of the title compound as beige crystals, mp>250° C.

後処理

  1. customThe mixture was transferred to a glass vessel
  2. customthe vessel was purged with N2
  3. customsealed
  4. temperatureThe reaction mixture was cooled
  5. concentrationconcentrated to dryness under reduced pressure
  6. customto give a golden solid
  7. customthe layers were separated
  8. concentrationThe organic layer was concentrated to dryness
  9. customto give a light-brown solid
  10. customthat was crystallized from acetonitrile

出典と根拠

ORDレコード
ord-6b01fb6209074455b681c170fea79026
出典データセット
uspto-grants-2012_06
特許番号
US08207162B2

関連ノート

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